In the United States alone, it is estimated that 60,130,000 patients have hypertension. Angiotensin I converting enzyme inhibitor (ACEI) are very popular and widely used in treating high blood pressure. These drugs are also often used in the treatment of diabetic kidney disease.
Approximately 12,000,000 people in the United States are estimated to have diabetes. It is already known in humans and animals that ACEI and other blood pressure-lowering drugs have a therapeutic effect on the kidney. The therapeutic effect is limited to only slowing down the effects of the disease. The mechanism of action on the kidney of these drugs is currently believed to be through their effect to lower the systemic pressure (i.e. blood pressure) and the pressures within the kidney micro-circulation. Both fluid pressures are commonly high in humans and animals with chronic kidney disease. Progression of glomerular sclerosis, the medical term for progressive kidney damage, is believed to result from a disruption of the dynamic balance between extracellular matrix synthesis and degradation of the mesangium. Recent in vivo studies by the inventors of the present invention and others have suggested that ACEI's effect of attenuating glomerular sclerosis is independent of its depressor action on systemic and glomerular pressures. Additionally, ACEI's suppressive effect on the extracellular matrix released from cultured mesangial cells has been demonstrated.
In view of the above, applicants have tested and demonstrated a potential benefit on glomerular sclerosis by using ACEI in a dose in excess of that required for normalization of systemic and glomerular pressures. In contrast to commonly held beliefs of the mechanism of action of ACEI, applicant's new observations implicate that patients with chronic renal disease, even without high blood pressure, will benefit from the administration of ACEI, particularly in high doses. This is because of ACEI's therapeutic effect on the kidney independent of its blood pressure controlling effect.